5-72223690-C-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_015084.3(MRPS27):c.998G>C(p.Arg333Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R333Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MRPS27
NM_015084.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.142

Publications

1 publications found

Variant links:

Genes affected

MRPS27 (HGNC:14512): (mitochondrial ribosomal protein S27) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 28S subunit protein that may be a functional partner of the death associated protein 3 (DAP3). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2013]

MRPS27 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3080838).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015084.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MRPS27	NM_015084.3	MANE Select	c.998G>C	p.Arg333Pro	missense	Exon 10 of 11	NP_055899.2	Q92552-1
MRPS27	NM_001286748.2		c.1040G>C	p.Arg347Pro	missense	Exon 11 of 12	NP_001273677.1	Q92552-2
MRPS27	NM_001286751.2		c.830G>C	p.Arg277Pro	missense	Exon 10 of 11	NP_001273680.1	G5EA06

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MRPS27	ENST00000261413.10	TSL:1 MANE Select	c.998G>C	p.Arg333Pro	missense	Exon 10 of 11	ENSP00000261413.5	Q92552-1
MRPS27	ENST00000695404.1		c.998G>C	p.Arg333Pro	missense	Exon 10 of 12	ENSP00000511886.1	A0A8Q3WKF1
MRPS27	ENST00000694998.2		c.1064G>C	p.Arg355Pro	missense	Exon 10 of 11	ENSP00000511636.2	A0A8Q3WK88

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251096

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461682

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727140

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33460

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111878

Other (OTH)

AF:

0.00

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Uncertain

0.067

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.055

Eigen

Benign

-0.091

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.24

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.033

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.6

PhyloP100

-0.14

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.26

Sift

Uncertain

0.021

Sift4G

Uncertain

0.0080

Polyphen

0.99

Vest4

0.62

MutPred

0.58

Loss of MoRF binding (P = 0.0065)

MVP

0.51

MPC

0.48

ClinPred

0.91

GERP RS

1.1

Varity_R

0.67

gMVP

0.75

Mutation Taster

=84/16

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over